反应详情

To a solution of 1-(2-(allyloxy)ethoxy)-2-bromo-5-chloro-4-(4-ethylbenzyl)benzene (AV) (1.74 g, 4.25 mmol) in anhydrous THF (10 mL) at −78° C., was added dropwise n-BuLi (2.9 M, 1.76 mL) and stirring was continued at −78° C. for 1 hour. The mixture was transferred to a solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)-tetrahydropyran-2-one (2.18 g, 4.68 mmol) in anhydrous THF (10 mL) at −78° C., and stirring was continued at −78° C. for 2 hours until the starting material was consumed. After quenching with methanesulfonic acid (1 g in 10 mL MeOH), the mixture was allowed to warm to room temperature and stirred overnight. H2O (20 mL) was added, and the organic phase was separated. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with saturated NaHCO3, water and brine, and then dried with anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography to provide crude product (0.8 g, Rf=0.1-0.2, EtOAc:PE=2:1). The crude product was dissolved in anhydrous CH3CN (10 mL), Et3SiH (1 mL) was added, the mixture was cooled to −5° C., and BF3.Et2O (0.6 mL) was added dropwise. The reaction was allowed to warm to 20° C. and stirred overnight. After the reaction was complete, it was quenched with saturated aqueous NaHCO3. The solvent was removed under vacuum and the residue was extracted with EtOAc and washed with water and brine. The residue was then dried with anhydrous Na2SO4, filtered and concentrated to give a solid, which was purified by preparative HPLC and freeze-dried to give final product AW as a white powder. 1H-NMR (CDCl3, 300 MHz) δ 7.34 (s, 1H), 7.07 (s, 4H), 7.04 (s, 1H), 5.96 (m, 1H), 5.28˜5.35 (m, 1H), 5.17˜5.22 (m, 1H), 4.54 (d, J=9.0 Hz, 1H), 4.03˜4.15 (m, 4H), 3.97 (d, J=2.1 Hz, 2H), 3.79˜3.87 (m, 2H), 3.62˜3.72 (m, 1H), 3.45˜3.51 (1,2H), 3.35˜3.44 (m, 2H), 3.29˜3.31 (m, 4H), 2.56 (q, J=7.5 Hz, 2H), 1.18 (t, J=7.5 Hz, 3H).

1. stirringstirring
2. waitwas continued at −78° C. for 2 hours until the starting material
3. customwas consumed
4. customAfter quenching with methanesulfonic acid (1 g in 10 mL MeOH)
5. stirringstirred overnight
6. additionH2O (20 mL) was added
7. customthe organic phase was separated
8. extractionThe aqueous phase was extracted with EtOAc
9. washThe combined organic phases were washed with saturated NaHCO3, water and brine
10. dry with materialdried with anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified by flash chromatography
14. customto provide crude product (0.8 g, Rf=0.1-0.2, EtOAc:PE=2:1)
15. temperaturethe mixture was cooled to −5° C.
16. temperatureto warm to 20° C.
17. stirringstirred overnight
18. customit was quenched with saturated aqueous NaHCO3
19. customThe solvent was removed under vacuum
20. extractionthe residue was extracted with EtOAc
21. washwashed with water and brine
22. dry with materialThe residue was then dried with anhydrous Na2SO4
23. filtrationfiltered
24. concentrationconcentrated
25. customto give a solid, which
26. customwas purified by preparative HPLC
27. customfreeze-dried